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Vol 22, No 2 (2025)

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Original studies

Biomarkers of T2 inflammation in the diagnosis and monitoring of eosinophilic esophagitis in children

Vyazankina S.S., Makarova S.G., Lokhmatov M.M., Murashkin N.N., Budkina T.N., Semikina E.L., Snovskaya M.A., Kurbatova O.V., Zhuzhula A.A., Fisenko A.P., Ereshko O.A., Ivanova V.M.

Abstract

BACKGROUND: Eosinophilic esophagitis is an immune-mediated disease associated with activation of T2 inflammation in esophageal tissues. Monitoring eosinophilic esophagitis activity in children requires invasive diagnostic methods using general anesthesia. The study of T2 inflammatory biomarkers is currently not a generally accepted diagnostic method but may be an informative and more accessible way to monitor eosinophilic esophagitis in children over time.

AIM: Comparative assessment of serum markers of T2 inflammation in children with eosinophilic esophagitis and other T2-associated diseases and determination of the potential of these biomarkers for monitoring the course of eosinophilic esophagitis.

MATERIALS AND METHODS: A cross-sectional, single-center comparative study included patients with eosinophilic esophagitis and other T2-associated diseases without eosinophilic esophagitis aged under 18 years. All patients underwent clinical and laboratory tests, esophagogastroduodenoscopy with morphological examination of esophageal mucosa biopsy specimens. Eosinophilic esophagitis activity was assessed using the I-SEE index. The concentrations of cytokines involved in the T2 type immune response were determined in blood serum using enzyme immunoassay.

RESULTS: The study included 80 patients: 40 patients with eosinophilic esophagitis, the comparison group included 40 children with other T2-associated diseases without eosinophilic esophagitis. Male patients were statistically significantly more common in the eosinophilic esophagitis group (p = 0.004). Immunoglobulin E- and non-immunoglobulin E-mediated food allergy were statistically significantly more common in patients with eosinophilic esophagitis (p = 0.003 and p = 0.002, respectively). The levels of interleukin 4 and 13 were statistically significantly higher in the comparison group (p <0.001). However, after dividing patients with eosinophilic esophagitis into subgroups by the degree of disease activity, in patients with low eosinophilic esophagitis activity, the level of interleukin 4, 13 and eotaxin-3 was statistically significantly lower (p <0.001). The level of eosinophil peroxidase was statistically significantly higher than in the comparison group and in patients with higher eosinophilic esophagitis activity and (p = 0.045 and p = 0.030, respectively). All patients with eosinophilic esophagitis complicated by esophageal stenosis had 15 or more points on I-SEE. The level of interleukin 33 in patients with esophageal stenosis was statistically significantly higher than in patients without stenosis (p <0.001).

CONCLUSION: Biomarkers of T2 inflammation demonstrated statistical significance in relation to the activity and severity of eosinophilic esophagitis. The obtained results highlight the high potential of using these biomarkers as a minimally invasive method for dynamic monitoring of disease activity, opening up new possibilities for a personalized approach to the treatment of eosinophilic esophagitis in children.

Russian Journal of Allergy. 2025;22(2):122-134
pages 122-134 views

Preclinical study of reproductive toxicity of a drug based on an aqueous solution of fullerene С60 for the treatment of food allergies

Kovaleva E.V., Ivanova Y.V., Onatsky N.M., Shangaraeva V.A., Gorshenin D.S., Baraboshkina E.N., Galkina A.A., Bolyakina D.K., Parshina V.A., Kurmasheva R.A., Shershakova N.N., Mikhina L.V., Khaitov M.R.

Abstract

BACKGROUND: The incidence of food allergy in adults and children is very high. The key approach in the therapy of food allergy can be quality drug selection. New synthetic derivatives of fullerene, a high-tech hydrocarbon, can become such drugs. A unique biocompatible method for obtaining a stable aqueous dispersion of fullerene C60 (ADF-C60) as the main component for drugs for the treatment of allergic diseases has been developed.

In this article, reproductive toxicity of the drug ADF-C60, currently in preclinical safety studies, was studied in female white outbred rats. Due to its properties, the ADF-C60 is promising for treatment of food allergy and can presumably be used during pregnancy.

AIM: Preclinical study of reproductive toxicity of an ADF-C60 in the antenatal and postnatal periods of rat offspring development with oral administration to the mother generation during pregnancy.

MATERIALS AND METHODS: Female rats were orally administered the ADF-C60 in 1-, 5-, and 50-fold therapeutic doses recommended for humans during the whole pregnancy. The general parameters of embryotoxic and teratogenic effects of the ADF-C60 before and after birth were studied.

RESULTS: No evidence of embryotoxic and teratogenic effects of the ADF-C60 was found during the study of gestational parameters and general fetuses development. No adverse effects of the ADF-C60 were revealed during observation of postnatal development of offspring.

CONCLUSION: ADF-C60 for the treatment of food allergy has no reproductive toxicity at doses up to 50 times higher than the therapeutic dose. After the conducted experiments it is possible to assume a significant probability of using the ADF-C60 during pregnancy, but additional preclinical and clinical studies are required to substantiate the obtained conclusion.

Russian Journal of Allergy. 2025;22(2):153-164
pages 153-164 views

ASIA syndrome masked as recurrent angioedema: сan development be predicted by genetic screening (pilot study)

Fomina D.S., Lebedkina M.S., Nikitina E.A., Kovalkova E.V., Andrenova G.V., Кruglova T.S., Bobrikova E.N., Markina U.A., Abdullaev S.P., Evsegneeva I.V., Karaulov A.V., Lysenko M.A.

Abstract

BACKGROUND: ASIA is an autoimmune/inflammatory syndrome induced by adjuvants. Symptoms can be diverse, and the recurrent angioedema is one of the dominant manifestations. Genetic screening is discussed as a preventive option. The following alleles of genes: HLA type II (DRB1*0301 or in combination with HLA-B*08, DRB1*01, and DRB4), as well as Arg620Trp polymorphism in the PTPN22 gene are discussed as a cause of autoimmune diseases, including ASIA syndrome.

AIM: To identify the presence of causative genetic factors in patients with ASIA syndrome by genetic screening, to identify adjuvants acting as a trigger, and to evaluate the efficacy of current therapy.

MATERIALS AND METHODS: A single center observational study of 16 patients with ASIA syndrome and 10 controls was performed. Genetic screening was performed in 14 patients from the ASIA group and 10 patients from the control group. Further inclusion of patients in the study is planned.

RESULTS: All patients with ASIA were women, potential triggers included hyaluronic acid fillers 10/16 (62.5 %), including in combination with breast silicone implants 1/16 (6.25 %), arthroplasty with shoulder joint replacement 1/16 (6.25 %), face hyaluronic acid injections 5/16 (31.25 %), and calcium hydroxyapatite 1/16 (6.25 %).

The main site of angioedema was the face 15/16 (93.75 %), also larynx (1/16 (6.25 %)), upper (2/16) and lower extremities (1/16 (6,25 %)). Other symptoms included arthralgia, myalgia, muscle weakness — 1/16 (6.25%), hypocomplementemic urticarial vasculitis, lymphocytic colitis — 1/16 (6.25 %), arthralgia combined with lymphadenopathy — 1/16 (6.25 %), chronic spontaneous and solar urticaria — 1/16 (6.25 %), fixed erythema of the shoulder skin with fever, antiphospholipid syndrome — 1/16 (6.25 %), normocomplementemic urticarial vasculitis — 1/16 (6.25 %), Still’s disease — 1/16 (6.25 %).

Autoimmune response was represented by autoantibodies in 10 (62.5 %) of 16 patients. Ten (62.5 %) patients received non-sedative antihistamines at standard and escalated doses (5 as monotherapy, 1 in combination with filler removal, 1 with hydroxychloroquine, 3 with hydroxychloroquine and omalizumab), 1 (6.25 %) received tranexamic acid, 1 (6.25 %) with danazol, 1 (6.25 %) with hydroxychloroquine, and 3 (18.75 %) patients received no therapy. A combination of two genetic factors was detected in 3 (21.4 %) patients: DRB1*0301, B1*08 (in 2 patients additionally Arg620Trp polymorphism). Isolated Arg620Trp polymorphism was detected in 6 (42.8 %) patients.

CONCLUSION: Genetic factors increasing the risk of autoimmune conditions were found in 9 out of 16 patients. No genetic abnormalities were found in the control group. More than half of the patients with ASIA syndrome had genetic factors associated with autoimmunity. Further studies are needed to create reliable diagnostic and treatment algorithms.

Russian Journal of Allergy. 2025;22(2):135-152
pages 135-152 views

Reviews

Approach to choosing antihistamines for treatment of itchy dermatoses

Nenasheva N.M., Nasunova A.Y.

Abstract

Every third patient who makes an appointment with a specialist (dermatologist or allergologist-immunologist) suffers from itchy dermatosis. Traditionally, in Russia this term includes such diseases as atopic dermatitis, contact dermatitis, eczema and urticaria. Pathogenesis of these diseases is based on immune-mediated skin inflammation characterized by itching of varying degrees of intensity. Itching can affect productivity, sleep quality and mood, aggravate skin diseases and lead to complications. Modern antihistamines are used to control itching as monotherapy or as an addition to topical treatment. Among non-sedating antihistamines, levocetirizine holds a special place with its favorable pharmacological profile. Rapid action and optimal duration of action in combination with low risk of drug interactions, good tolerability, absence of influence on cognitive and psychomotor functions and cardiac safety make levocetirizine the drug of first choice in treatment of skin itching in itchy dermatoses. Real practice confirms the claimed characteristics of the medicine.

Russian Journal of Allergy. 2025;22(2):165-178
pages 165-178 views

Epigenetics and its role in development and regulation of allergy — a systematic review

Jain S.K., Sharma S., Singh V.K., Rani R.

Abstract

BACKGROUND: Epigenetic mechanisms involving DNA methylation, histone modifications, and non-coding RNAs have more recently been highlighted as important regulatory elements of gene expression in allergic diseases. Such mechanisms mediate interactions between predisposing genetic determinants and environmental exposures, with subsequent influences on immune response as well as on susceptibility to conditions such as asthma, allergic rhinitis, atopic dermatitis, and food allergies.

MATERIALS AND METHODS: This systematic review integrated evidence from studies exploring the role of epigenetic modifications in allergic diseases. The databases were searched systematically and relevant studies as per predefined PECOS criteria were included. All data regarding epigenetic mechanisms, the target loci involved, environmental influences, and allergic outcomes were extracted and analyzed. The studies were evaluated for risk of bias using the RoB 2.0 and ROBINS-I tools, and the certainty of evidence was appraised using the GRADE framework.

RESULTS: It was observed that DNA methylation at such loci, including FOXP3 and IL-4Rα, was invariably associated with immune dysregulation in allergic diseases across the 11 studies included. Exposure to pollutants and microbial exposure has shown associations with alterations in epigenetic profiles that have resulted in significant impacts on immune tolerance and allergic inflammation. Quantitative results: in specific immunotherapy settings, 95 % suppression of effector T-cell proliferation (p <0.0001), and identification of 956 CpG sites associated with the risk of allergic rhinitis Fixed drug reaction (FDR) <5 %. The studies together showed that epigenetic modifications are central to the pathogenesis of allergic diseases and may be used as biomarkers and therapeutic targets.

CONCLUSION: This review highlighted how epigenetics played a crucial role in the development and regulation of allergic diseases and underlined the interactions between these entities and environmental exposures. Findings indicated that epigenetic mechanisms promise a wide potential in precision medicine, mainly concerning biomarker discovery and treatment stratification. However, study methodology heterogeneity and variability of results should be pursued further for homogenization of methodologies and thus increasing the applicability in clinics.

Russian Journal of Allergy. 2025;22(2):179-194
pages 179-194 views

Current aspects of the use of allergen-specific immunotherapy in patients with bronchial asthma: review of GINA 2024 updates and results of the EfficAPSI study

Kurbacheva O.M., Ilyina N.I., Namazova-Baranova L.S., Nenasheva N.M., Fedenko E.S., Kleiner D.V.

Abstract

Bronchial asthma remains one of the most significant respiratory diseases in the world and in Russia. The number of patients with asthma is steadily increasing, and disease control is not achieved in all patients, even with adequate pharmacotherapy.

The only currently available method for the treatment of respiratory allergy that can influence the natural course of the disease is allergen-specific immunotherapy. Studying the impact of allergen-specific immunotherapy on asthma onset and progression is critical to optimizing current treatment strategies and providing new and unique options for patients with asthma. Scientific communities are focused on promoting disease-modifying solutions based on compelling clinical evidence to rethink approaches to the treatment of respiratory diseases and improve the quality of life of people with allergies. The updated Global Initiative for Asthma 2024 guidelines emphasize the importance of allergen-specific immunotherapy, especially sublingual form, in the management of allergic asthma, noting its ability to reduce the risk of onset and progression of the disease.

The article examines the main provisions of the new expert guidelines in the field of allergen-specific immunotherapy and presents the results of the EfficAPSI study, one of the largest population-based studies demonstrating the effect of sublingual immunotherapy on the course of asthma.

Russian Journal of Allergy. 2025;22(2):195-206
pages 195-206 views

Clinical efficacy and safety of fixed-dose intranasal combination of azelastine hydrochloride and fluticasone propionate for treatment of seasonal allergic rhinitis

Nenasheva N.M., Sebekina O.V., Peredelskaya M.Y.

Abstract

Allergic rhinitis is a common chronic respiratory disease that affects millions of people worldwide and has a significant impact on their quality of life, productivity, and performance. Achieving control of the symptoms of moderate/severe allergic rhinitis, which often requires the use of several drugs from different pharmacological groups, is particularly challenging.

The article considers clinical efficacy and safety of fixed-dose intranasal combination of azelastine hydrochloride and fluticasone propionate for treatment of seasonal allergic rhinitis. The combination of azelastine hydrochloride and fluticasone propionate demonstrates a synergistic effect in improving the symptoms of both early and late allergic reactions and has a pronounced anti-inflammatory effect. Studies show that the use of fixed-dose combination of azelastine hydrochloride and fluticasone propionate significantly improves nasal and ocular symptoms of seasonal allergic rhinitis compared to fluticasone propionate and azelastine hydrochloride monotherapies. The drug acts quickly and provides sustained relief of symptoms which contributes to improved quality of life for the patients.

The article provides an overview of the main preclinical, clinical randomized trials and studies in real clinical practice on the efficacy and safety of the fixed-dose intranasal combination, especially in comparison with monotherapies with the drugs included in the combination and placebo. It demonstrates its effectiveness in different populations regardless of race, gender and age, and in long-term use. Azelastine hydrochloride in combination with fluticasone propionate has the most extensive body of evidence of its efficacy, including studies conducted in the Russian patient population. The drug can be used in patients from the age of 12 years with moderate to severe seasonal allergic rhinitis. It is included in all international and Russian guidelines on allergic rhinitis.

Russian Journal of Allergy. 2025;22(2):207-216
pages 207-216 views

Case reports

Vasculitis with nervous system damage in a patient with adenosine deaminase 2 deficiency

Golovina O.A., Roppelt A.A., Markina U.A., Mutovina Z.Y., Shishimorov A.A., Schukin K.A., Karaulov A.V., Lysenko M.A., Fomina D.S.

Abstract

Deficiency of adenosine deaminase 2 is a rare monogenic disease, inherited in an autosomal recessive manner and caused by a loss-of-function mutation in the ADA2 gene. The disease is manifested by systemic vasculitis, deficiency of bone marrow failure, and/or immunodeficiency. According to international classification of inborn errors of immunity, deficiency of adenosine deaminase 2 is considered to be an autoinflammatory syndrome. Most often, the disease debuts before the age of 18, however, debuts at an older age have been reported. Due to nonspecificity of the symptoms, the correct diagnosis can be quite late, and patients can end up consulting a number of specialists besides a pediatrician or an immunologist. A delay in diagnosis, in turn, delays the start of therapy of the underlying disease, which determines the prognosis of the disease, and affects patients’ quality of life.

In this article, we present a literature review on deficiency of adenosine deaminase 2 and a clinical case with a prevailing clinical picture of vasculitis with nervous system damage, which demonstrates the importance of timely diagnosis and the relevance of knowledge of the disease by doctors of different specialties.

Russian Journal of Allergy. 2025;22(2):217-225
pages 217-225 views

Letters to the editor

The past, present, and future of anti-IgE therapy

Nenasheva N.M., Kurbacheva O.M., Fedenko E.S.

Abstract

Immunoglobulin E is the last of the discovered immunoglobulins and is the main mediator of allergic reactions. Its role in allergy pathogenesis led to development of the first immunobiological drug for treatment of allergic diseases — omalizumab. Omalizumab binds free immunoglobulin E, preventing its binding to high-affinity receptors, thereby blocking the cascade of allergic inflammation.

This review discusses the results of the main studies of omalizumab for treatment of severe bronchial asthma, chronic spontaneous urticaria, and other allergic diseases. The drug has been used for more than twenty years, but the research is still ongoing. Thus in 2024, omalizumab was approved for use in prevention of anaphylaxis in patients with food allergies. The drug is being studied in combination with allergen-specific immunotherapy, as well as in patients with allergic bronchopulmonary aspergillosis.

Russian Journal of Allergy. 2025;22(2):226-232
pages 226-232 views

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